# US 11,433,075 B2 · Methods of treating glioblastoma

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- Number: US 11,433,075 B2
- Document ID: US11433075B2
- Status: Granted
- Kind: B2
- Application number: 17/152,506
- Filed: 2021-01-19
- Published: 2021-05-13
- Granted: 2022-09-06
- Earliest claimed: 2017-06-22
- Assignees: Triact Therapeutics, Inc.
- Applicants: TriAct Therapeutics, Inc.
- Inventors: Thomas F. White
- Web page: https://patentgrep.com/patent/US11433075B2

## CPC

- A61K 31/522: having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
- A61P 35/00: Antineoplastic agents
- C12Q 1/6827: for detection of mutation or polymorphism
- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
- C12Q 2600/154: Methylation markers
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES

## Abstract

Disclosed herein are methods and compounds for treating glioblastoma with iniparib. Also disclosed herein is a method of selecting subjects having a glioblastoma for treatment based on a biomarker panel.

## Claims

### Claim 1

A method of treating glioblastoma in a human subject in need thereof, wherein a biological sample from said human subject comprises a presence of methylation at a promoter region of an MGMT gene, the method comprising:
administering to the human subject (i) about 5 milligrams per kilogram (mg/kg) to about 10 mg/kg of 4-iodo-3-nitrobenzamide or a salt, metabolite or prodrug thereof, (ii) about 75 milligrams per square meter (mg/m2) to about 200 mg/m2 of temozolomide, and (iii) 0 up to about 60 total grays (Gy) radiation.

### Claim 2 (depends on 1)

The method of claim 1, wherein the 4-iodo-3-nitrobenzamide or the salt, metabolite or prodrug thereof is administered to the human subject in an amount of about 8 mg/kg.

### Claim 3 (depends on 2)

The method of claim 2, wherein the 4-iodo-3-nitrobenzamide or the salt, metabolite or prodrug thereof is administered to the human subject once a day and twice a week.

### Claim 4 (depends on 3)

The method of claim 3, wherein the 4-iodo-3-nitrobenzamide or the salt, metabolite or prodrug thereof is administered to the human subject for about six weeks.

### Claim 5 (depends on 1)

The method of claim 1, wherein temozolomide is administered to the human subject in an amount of about 75 mg/m2.

### Claim 6 (depends on 5)

The method of claim 5, wherein temozolomide is administered to the human subject daily.

### Claim 7 (depends on 6)

The method of claim 6, wherein temozolomide is administered to the human subject for about six weeks.

### Claim 8 (depends on 1)

The method of claim 1, wherein about 60 Gy of radiation is administered to the human subject over a course of about six weeks.

### Claim 9 (depends on 1)

The method of claim 1, wherein upon completion of about six weeks of treatment with 4-iodo-3-nitrobenzamide or the salt, metabolite or prodrug thereof, temozolomide, and radiation, the human subject receives a treatment break of about four weeks.

### Claim 10 (depends on 1)

The method of claim 1, further comprising a maintenance regimen comprising administering (i) about 5 mg/kg to about 10 mg/kg of 4-iodo-3-nitrobenzamide or the salt, metabolite or prodrug thereof, (ii) about 70 mg/m2 to about 200 mg/m2 of temozolomide.

### Claim 11 (depends on 10)

The method of claim 10, wherein the 4-iodo-3-nitrobenzamide or the salt, metabolite or prodrug thereof is administered to the human subject in an amount of about 8.6 mg/kg.

### Claim 12 (depends on 10)

The method of claim 10, wherein the 4-iodo-3-nitrobenzamide or the salt, metabolite or prodrug thereof is administered to the human subject once a day and twice a week.

### Claim 13 (depends on 12)

The method of claim 12, wherein temozolomide is administered to the human subject in an amount of about 150 mg/m2 to about 200 mg/m2.

### Claim 14 (depends on 12)

The method of claim 12, wherein the 4-iodo-3-nitrobenzamide or the salt, metabolite or prodrug thereof and the temozolomide is administered to the human subject for about 1-6 cycles, wherein a single cycle is about 28 days.

### Claim 15 (depends on 14)

The method of claim 14, wherein the temozolomide is administered to the human subject on Days 1-5 of each cycle.

### Claim 16 (depends on 1)

The method of claim 1, wherein the 4-iodo-3-nitrobenzamide or the salt, metabolite or prodrug thereof is formulated for parenteral administration, wherein the parenteral administration comprises intravenous, intra-arterial, intracranial, intracerebral, intracerebroventricular, or intrathecal administration.

### Claim 17 (depends on 1)

The method of claim 1, wherein the 4-iodo-3-nitrobenzamide or the salt, metabolite or prodrug thereof is formulated as an injection or as an infusion.

### Claim 18 (depends on 1)

The method of claim 1, wherein the glioblastoma is a primary glioblastoma or a secondary tumor.

### Claim 19 (depends on 1)

The method of claim 1, wherein the human subject has a grade III or grade IV glioblastoma.

### Claim 20 (depends on 1)

The method of claim 1, wherein the method further comprises prior to administering, determining whether the human subject comprises the presence of methylation at the promoter region of the MGMT gene by obtaining the biological sample from the human subject, and performing a methylation assay on the biological sample to determine if the human subject has the presence of methylation at the promoter region of the MGMT gene.
